Interview with Dr. Mary Beckerle for Sarcoma Awareness Month

Mary BeckerleTo recognize Sarcoma Awareness Month, we asked Mary Beckerle, PhD, CEO and Director of the Huntsman Cancer Institute at the University of Utah, member of the Cancer Moonshot Blue Ribbon Panel and Acceleration Initiative I grantee, about her work testing a novel targeted treatment for Ewing sarcoma.

Q. What kind of research are you doing involving sarcoma?

A. Our team at Huntsman Cancer Institute is developing a collaborative project centered on a novel targeted treatment for Ewing sarcoma that we hope will disrupt the development, growth, and spread of this type of cancer. Ewing sarcomas develop because of a chromosomal abnormality that results in the expression of EWS/FLI, a protein that is not usually produced. When EWS/FLI is present, thousands of genes are aberrantly expressed, which typically affects a large number of cellular processes.

Watch this video to learn more:


In previous work, we found that one of the effects of EWS/FLI is to disrupt the intracellular skeleton, which compromises the ability of cells to adhere (stick to) and remain in their normal environment. As a result, cells are more likely to travel to another area of the body, which makes it easy for tumors to spread. In addition, we have used state-of-the-art approaches to study the consequences of preventing expression of EWS/FLI in cells isolated from Ewing Sarcoma patients.

We were very excited when we found that the absence of EWS/FLI changed tumor cells into apparently healthy cells, and also restored normal adhesion.

Our current model is shown below:

Ewing Sarcoma ModelModel of EWS-FLI-dependent induction of Ewing sarcoma and restoration of cellular health following suppression of EWS-FLI. Modified from Chaturvedi et al., Genes & Cancer 2012, 3(2) 102–116


In patients, Ewing sarcoma arises in bone. Thus, we designed and implemented a model based on injecting Ewing sarcoma cells directly into the mouse leg bones [Chaturvedi et al., Mol Biol Cell 2014, 25(18): 2695–2709]. This strategy provided us with a robust Ewing sarcoma mouse model that faithfully recapitulates key clinical features of the human disease. We then thought that if we could stop the pro-carcinogenic actions of EWS/FLI, cancer development and spreading might also stop in the animals.

It is difficult to target EWS/FLI directly, but an equally effective strategy is to inhibit an enzyme called lysine specific demethylase 1 (LSD1) that regulates EWS/FLI. We developed a new inhibitor (HCI 2577), tested it in our mouse model, and were excited to find that HCI 2577 significantly suppressed tumor progression. We have scaled up the manufacture of clinical grade HCI2577 and we are assessing its safety in our animal models before conducting clinical trials in humans, projected to begin in 2016/2017.

Q. Why are you interested in finding a cure for sarcoma?

A. There are unmet needs for this condition, and we want to use the resources we have, including the expertise of our team, to tackle this problem. Ewing sarcoma is the second most common bone cancer in children and a challenging disease to treat because it has typically spread to other organs by the time of diagnosis. Children diagnosed with Ewing sarcoma are treated using surgical and chemotherapeutic approaches but, unfortunately, many children will relapse with metastatic disease, which decreases the chances of survival.

We want to change the outcome for children with metastatic Ewing sarcoma. If our work is successful, we will have developed a new treatment that stops Ewing sarcoma in its tracks and will be able to improve survival of these high-risk children.

Q. What is your proudest accomplishment so far in regards to your research?

A. Our potential for success as we advance and develop novel strategies to diagnose, manage and treat challenging diseases such as cancer depends on our ability to cross boundaries and establish fruitful collaborations with experts in diverse disciplines. I have drawn much enjoyment from bringing together a team of cell biologists, oncologists, and pharmacologists with expertise in drug development. We were able to come together as a team to identify the best strategies to answer our Ewing Sarcoma questions ― including the development of a promising therapeutic.

Q. What advice would you give to a child with cancer?

A. The answer to this question is, of course, dependent on the age of the child, but in general, I think that a child with cancer can draw significant benefit from networks of supporting peers who are facing similar challenges. I would encourage the child to seek and then maintain these associations.

Children have a way of communicating with one another that can have important beneficial effects therapeutically and emotionally. Some cancer treatment centers offer strategies that facilitate the ability of children to achieve this goal. I would also advise a child to ask friends to visit frequently, express feelings openly, and take control of her/his situation. Taking the time to rest well and adhering to a healthy diet is fundamental for therapeutic efficacy and to adequately tolerate side effects that can otherwise be quite debilitating, both physically and emotionally.

Q. What advice would you give to parents of children dealing with sarcoma?

A. When I am asked this question, I like to provide advice based on the experiences of those who have directly dealt with this challenge and can offer solutions that work; in fact, much research has been devoted to this important issue. I think it is very clear that establishing healthy relationships with the treatment team and developing a good understanding of the characteristics of the particular sarcoma affecting the child, is essential. This approach is contextually helpful for the parents’ ability to place a specific diagnosis and treatment options in perspective. It can provide a framework to support the decision-making process, and can be enormously helpful to limit psychological distress and maximize coping and adaptation.

Additionally, an environment that is inclusive of supportive family and friends can be very useful. Being as aware as possible of the present by embracing those days when everything is going well, can provide strength for more challenging events down the road.

Remaining positive and hopeful, staying focused, persevering, and making efforts to stay active can significantly and positively impact children and parents.

Huntsman Cancer Institute Ewing Sarcoma Team
Ewing sarcoma team at Huntsman Cancer Institute: from left to right: Stephen Lessnick, M.D., Ph.D.; Alana Welm, Ph.D.; Mary Beckerle, Ph.D.; Sunil Sharma, M.D.


CureSearch supports the work of Dr. Beckerle and other Acceleration Initiative grantees dedicated to finding cures for children with cancer. To learn more about their work, click here.

Want more stories like this?

Get emails that matter, when it matters.

Please leave this field empty


Pin It on Pinterest

Scroll to Top